The purpose of the proposed project is to elucidate those factors regulating the biosynthesis and catabolism of secretory (mucin) and membrane glycoproteins and secretion of secretory glycoproteins in cells obtained from normal subjects and from C.F. patients. Such information is necessary for further elucidating the pathogenic mechanisms in cystic fibrosis. Eventually to achieve the general aim of this proposal, specific essential information must be sought. We plan to study enzymes involved in the biosynthesis and catabolism of glycoproteins to learn the mode of regulation of membrane and secretory glycoprotein metabolism in the normal cells and cells obtained from the patients with cystic fibrosis. We also plan to investigate the secretion and metabolism of these glycoproteins by analyzing the cells and the incubation media following the pulse labelling of the cells with sugar precursors. The effects of blood, saliva and culture media containing substances secreted from cells from cystic fibrosis patients as well as other substances on the cells from normal subjects and also on cells isolated from rats and rabbits will be studied utilizing similar methods as described above.